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Antibiotics
Topics
- Antimicrobial Therapy
- Selective Toxicity
- Survey of Antimicrobial Drugs
- Microbial Drug Resistance
- Drug and Host Interaction
Key Words
Sterilization/disinfection/antisepsis
Antibiotic
Selective toxicity
Bactericidal
Bacteriostatic
Penicillinase/beta lactamas
Resistance
3
Selective Toxicity
Semmelweis
Antibiotics
History
Ancient remedies
Ehrlich
Domagk
Fleming
Neem Plant
11
Neem Plant
12
Propolis
13
Propolis
Selman Waksman
18
14
12
Resistance
16
10
8
6
4
2
1983-87
1988-92
1993-97
1998-02
2003-05
2008
Bars represent number of new antimicrobial agents approved by the FDA during the period listed.
Infectious Diseases Society of America. Bad Bugs, No Drugs. July 2004; Spellberg B et al. Clin Infect Dis. 2004;38:1279-1286;
New antimicrobial agents. Antimicrob Agents Chemother. 2006;50:1912
Azamulin
21
Linezolid
Solubility
Tissue stability
Selective toxicity
Resistance
Acquisition
Stable toxicity
level
Shelf Life
Allergenicity
Cost
ANTIBIOTICS
Selectively toxic for bacteria
bactericidal (killing)
bacteriostatic (growth inhibition)
no harm to patient
28
Antibiotic/Antimicrobial
Antibiotic:
Chemical produced
by a microorganism that kills or
inhibits the growth of another
microorganism
Antimicrobial agent: Chemical
that kills or inhibits the growth of
microorganisms
Microbial
Sources
of
Antibiotics
Administration of Antibiotics
31
Spectrum of Activity
Disk Diffusion
Method
Dilution Method
Serum Killing
Power
Automated
Methods
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
Natural penicillins
Narrow range of action
Susceptible to penicillinase (b lactamase)
Antibiotics weaken the cell wall, and cause the cell to lyse.
Penicillin
Penicillin chrysogenum
A diverse group (1st, 2nd , 3rd generations)
Natural (penicillin G and V)
Semisynthetic (Ampicillin, Carbenicillin)
Structure
Thiazolidine ring
Beta-lactam ring
Variable side chain (R group)
44
Penicillins
Figure 20.6
Semisynthetic Penicillins
Penicilinase-resistant penicillins
Carbapenems: very broad spectrum
Monobactam: Gram negative
Extended-spectrum penicillins
Penicillins + b-lactamase inhibitors
Penicillinase (b Lactamase)
Cephalosporins
2nd, 3rd, and 4th
generations more
effective against
gram-negatives
Figure 20.9
Cephalosporin
Cephalosporium acremonium (mold)
Widely administered today
Diverse group (natural and
semisynthetic)
Structure
similar to penicillin except
Main ring is different
Two sites for R groups
The different
R groups
allow for
versatility
and improved
effectiveness.
Mycobacteria:
interfere with
mycolic acid
synthesis or
incorporation
Isoniazid (INH)
Ethambutol
Polypeptide antibiotics
Bacitracin
Topical application
Against gram-positives
Vancomycin
Glycopeptide
Important "last line" against antibiotic resistant S.
aureus
Aminoglycosides: Streptomycin,
neomycin, gentamycin
Tetracyclines
Macrolides: Erythromycin
Chloramphenicol
Aminoglycosides
From Streptomyces
Inhibit protein synthesis
Tetracycline
Inhibits proteins synthesis
Broad spectrum and low cost
Commonly used to treat sexually
transmitted diseases
Minor side effect gastrointestinal
disruption
Tetracyclines
(bacteriostatic)
Resistance - Common
70
Spectinomycin
(bacteriostatic)
Erythromycin
Chloramphenicol
Broad-spectrum
Treat typhoid fever, brain abscesses
Rarely used now due to side effects
aplastic anemia
Chloramphenicol
UDP-glucuronyl transferase
Aminoglycoside
Rifampin binds to
DNA-dependent
RNA polymerase
and inhibits
intiation of RNA
synthesis
Antibacterials Antimetabolites
Sulfonamides
Isoniazid
Ethambutol
Nitrofurans
Competitive Inhibitors
Sulfonamides (Sulfa drugs)
Inhibit folic acid synthesis
Broad spectrum
Figure 5.7
98
Necrotizing Fasciitis
Summary of Targets
Antibiotic Resistance
Figure 20.20
Antimicrobial Resistance
Relative
or complete lack of
effect of antimicrobial against
a previously susceptible
microbe
Increase in MIC
Mechanisms of Antibiotic
Resistance
Enzymatic destruction of drug
Prevention of penetration of drug
Alteration of drug's target site
Rapid ejection of the drug
to sub-optimal
levels of antimicrobial
Exposure to microbes
carrying resistance genes
Antibiotics in Foods
Consequences of
Antimicrobial Resistance
Infections
resistant to
available
antibiotics
Increased cost
of treatment
Multi-Drug Resistant TB
MRSA mer-sah
Methicillin-Resistant
Staphylococcus aureus
Most frequent nosocomial
(hospital-acquired) pathogen
Usually resistant to several
other antibiotics
Antimicrobial peptides
Broad spectrum antibiotics from
plants and animals
Squalamine (sharks)
Protegrin (pigs)
Magainin (frogs)
Side Effects
Resistance to Drugs
Chromosomal
Plasmid borne
Enzyme development
Generations of Drugs
First/Second/Third
Line Drugs
Cross Resistance
Antibiotic Resistance
Mechanisms of Resistance
Drug Resistance
Resistance Genes
Integrons
Mechanism of Transfer
Origin of resistance
Gene expression
Resistance
enzymes that
permanently alter drug
structure (beta lactamases)
Resistance
PUMPS
Antimicrobial Resistance:
Key Prevention Strategies
Susceptible Pathogen
Antimicrobial-Resistant Pathogen
Prevent
Transmission
Prevent
Infection
Infection
Antimicrobial
Resistance
Effective
Diagnosis
and Treatment
Optimize
Use
Antimicrobial Use
12 Steps to Prevent
Antimicrobial Resistance:
Hospitalized Adults
12 Contain your contagion
11 Isolate the pathogen
10 Stop treatment when cured
9 Know when to say no to vanco
8 Treat infection, not colonization
7 Treat infection, not contamination
6 Use local data
5 Practice antimicrobial control
4 Access the experts
3 Target the pathogen
2 Get the catheters out
1 Vaccinate
Prevent
Transmission
Use Antimicrobials
Wisely
Diagnose and Treat
Effectively
Prevent Infection
Vancomycin-resistant
enterococci
Conjugative transposons
Responsible for at
least as much
resistance gene
transfer as
plasmids,
especially among
G+, and they have a
broad host range
G+ G+ ; G - G - ;
G+ G -
157